The application of photodynamic therapy (PDT) in oncology relies upon the use of a photosensitizer to produce reactive oxygen species (ROS), such as singlet oxygen, 1O2, to destroy cancer cells by terminally modifying the bio-molecules they interact with [Calin, M. A. et al. (2006) Photodynamic therapy in oncology, J. Optoelect. Adv. Mat. 8, 1173-1179; Thierry Patrice. Photodynamic Therapy; Royal Society of Chemistry, 2004].
A photosensitizing agent, such as ground state, singlet phthalocyanine (Pc), 1Pc, absorbs light to generate a triplet excited state, 3Pc, that in turn transfers its energy to ground state triplet oxygen, 3O2, to produce excited state singlet oxygen, 1O2, and regenerate the 1Pc [Ishii, K. (2012) Functional singlet oxygen generators based on phthalocyanines, Coord. Chem. Rev. 256, 1556-1568]. Pcs absorb light strongly in the red and near-infrared regions of the electromagnetic spectrum, 600-1000 nm, favorable for benign tissue penetration. This effect stimulates 1O2 production in an aerobic tumor microenvironment, ultimately leading to programmed cancer cell death [Josefsen, L. B. et al. (2012) Unique diagnostic and therapeutic roles of porphyrins and phthalocyanines in photodynamic therapy, imaging and theranostics, Theranostics 2, 916-966].
Cancer-targeting Pc photosensitizers have been shown to enhance the efficiency of the PDT response in tumor cells while reducing their side effects [(a) Master, A. et al. (2013) A cell-targeted photodynamic nanomedicine strategy for head and neck cancers, Mol Pharm. 10, 1988-1997, (b) Sibrian-Vazquez, M. et al. (2007) Synthesis and properties of cell-targeted Zn(II)-phthalocyanine-peptide conjugates, Bioconjug Chem. 18, 410-420, (c) Ranyuk, E. et al. (2013) Phthalocyanine-peptide conjugates: receptor-targeting bifunctional agents for imaging and photodynamic therapy, J Med Chem. 56, 1520-1534, (d) Ongarora, B. G. et al. (2012) Phthalocyanine-peptide conjugates for epidermal growth factor receptor targeting, J Med Chem. 55, 3725-3738, (e) Ke, M. R. et al. (2012) A phthalocyanine-peptide conjugate with high in vitro photodynamic activity and enhanced in vivo tumor-retention property, Chemistry 18, 4225-4233, (f) Huang, L. et al. (2008) Photochemical DNA cleavage by novel water-soluble sulfonated dihydroxy phosphorus(V) tetrabenzotriazacorrole, Bioorg Med Chem Lett. 18, 2152-2155, (g) Kuznetsova, A. A. et al. (2008) DNA-binding and oxidative properties of cationic phthalocyanines and their dimeric complexes with anionic phthalocyanines covalently linked to oligonucleotides, J Biomol Struct Dyn. 26, 307-320, (h) Erdem, S. S. et al. (2009) Mono-amine functionalized phthalocyanines: microwave-assisted solid-phase synthesis and bioconjugation strategies J Org Chem. 74, 9280-9286, (i) Nesterova, I. V. et al. (2007) Metallo-phthalocyanine near-IR fluorophores: oligonucleotide conjugates and their applications in PCR assays, Bioconj Chem. 18, 2159-2168].
Diagnostic applications of a Pc photosensitizer relies on its ability to absorb and emit light in the visible/near infrared region (400-900 nm) for instrumental detection [Nesterova, I. V. et al. (2009) Phthalocyanine Dimerization-Based Molecular Beacons Using Near-IR Fluorescence, J. Am. Chem. Soc. 131, 2432-2433] and diagnosis of a disease state [Master, A. et al. (2014) A Cell-Targeted Photodynamic Nanomedicine Strategy for Head and Neck Cancers, Mol. Pharm. 10, 1988-1997].
Despite the above described advances in the art, still further improvements in the Pcs and their methods of use in diagnostic applications and disease treatment would be desirable.